Re-Radiochemotherapy and Pembrolizumab vs. Immuno(Chemo)Therapy for Locoregionally Recurrent PD-L1 Positive (CPS≥1) HNSCC

NCT07026474 | Recruiting Phase 3 DMC

• 2 other identifiers: RePaIr-HN2024-520264-33-00
• Study Type: interventional
• Target: 214
• Locations: 1 country
• Sites: 18

Brief Summary

Prospective, open-label, randomized controlled phase III trail that aims to investigate whether Re-Radiochemotherapy (Re-RCT) and sequential immunotherapy with pembrolizumab improves overall survival compared to the standard treatment with pembrolizumab alone (± chemotherapy) in locoregionally recurrent PD-L1 positive (CPS≥1) HNSCC.

Conditions

Recurrent Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  To evaluate the efficacy of a sequential treatment of Re-RCT followed by pembrolizumab compared to standard therapy with pembrolizumab ± chemotherapy, the primary endpoint of the trial is overall survival rate at 2 years.

  2 years

Study Arms (2)

Investigational arm

EXPERIMENTAL

Patients receive Re-RCT followed by pembrolizumab immunotherapy for up to 2 years. Concomitant chemotheraphy is cisplatin. In case of renal dysfunction cisplatin can be switched to carboplatin.

Other: radiotherapy; Drug: Cisplatin; Drug: Alternative medications: carboplatin; Drug: Pembrolizumab

Control arm

ACTIVE COMPARATOR

Patients receive pembrolizumab monotherapy for up to 2 years. At the discretion of the treating physician, up to 6 additional cycles of cisplatin or carboplatin in combination with 5-fluorouracil may be given.

Drug: Pembrolizumab; Drug: cisplatin + 5-fluorouracil (5FU); Drug: Alternative medications: carboplatin + 5-fluorouracil (5FU)

Interventions

radiotherapy OTHER

single doses of 1.8Gy up to a total dose of 55.8Gy to 63.0Gy

Investigational arm

Cisplatin DRUG

40mg/m² BSA weekly concomitant to re-irradiation

Investigational arm

Alternative medications: carboplatin + 5-fluorouracil (5FU) DRUG

Carboplatin: AUC5 d1, q3w / 5-FU: 1000mg/m² BSA d1-4, q3w

Control arm

cisplatin + 5-fluorouracil (5FU) DRUG

Cisplatin: 100mg/m² BSA d1, q3w / 5-FU: 1000mg/m² BSA d1-4, q3w

Control arm

Alternative medications: carboplatin DRUG

AUC2 weekly

Investigational arm

Pembrolizumab DRUG

i.v., 200mg absolute, q3w

Control arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained from the subject prior to performing any protocol-related procedures.
• Age ≥ 18 years at time of study entry.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
• Locoregionally recurrent or second primary HNSCC.
• Histological confirmation of HNSCC.
• Tumor is surgically not resectable or surgical resection bears great potential for relevant functional morbidity or patient refuses surgery.
• No distant metastases (cM0).
• PD-L1 combined positive score (CPS) ≥1 according to local pathological PD-L1 assessment. A validated test must be used in an accredited laboratory.
• Prior radio(chemo)therapy of the neck (time interval ≥ 6 months).
• Adequate normal organ and marrow function as defined: Haemoglobin ≥ 9.0 g/dL; Leukocytes (WBC) ≥ 3,000 per mm3or Neutrophils ≥ 1,500 per mm3; Platelet count \> 100,000 per mm3.
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of haemolysis or hepatic pathology).
• AST (SGOT) / ALT (SGPT) ≤ 2.5 x institutional ULN.
• Creatinine Clearance ≥ 40ml/min (calculated from serum creatinine using the Cockcroft-Gault formula).
• Female subject of childbearing potential should have a negative serum pregnancy within 72 hours prior to receiving the first dose of RT and/or the first dose of pembrolizumab. A highly sensitive pregnancy test must be used.
• Female subjects of childbearing potential must be willing to use a highly effective contraceptive measure (see also Section 7.1.9 Contraception and pregnancy testing during the trial). Highly effective contraception is required for the course of the trial through 120 days after the last dose of trial therapy.

You may not qualify if:

• Prior radio(chemo)therapy of the neck less than 6 months ago.
• Distant metastases (cM1).
• Is currently participating and receiving trial therapy or has participated in a trial of an investigational agent and received trial therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of trial treatment. The following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• Prior chemotherapy or targeted small molecule therapy within 2 weeks or anti-cancer monoclonal antibody (mAb) within 4 weeks prior to trial day 1 or who has not recovered from AEs due to a previously administered agent. (Subjects with ≤ grade 2 neuropathy are an exception to this criterion and may qualify for the trial.)
• History or concurrent other malignancy. Exceptions include patients, who have been disease free for at least 3 years. Further exceptions are completely resected basal cell carcinoma or squamous cell carcinoma of the skin or successfully treated in situ carcinoma.
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• History of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Has an active or chronic infection requiring systemic antibacterial, antifungal or antiviral therapy within 14 days prior to randomization or first dose of study drugs.
• Known hypersensitivity to the active substances or to any of the excipients.
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Sponsors & Collaborators

• Universität des Saarlandes: lead

Study Sites (18)

Klinikum Chemnitz gGmbH, Klinik für Radioonkologie

Chemnitz, 09116, Germany

RECRUITING

Klinikum Darmstadt GmbH, Institut für Radioonkologie und Strahlentherapie

Darmstadt, 64283, Germany

RECRUITING

Gemeinschaftspraxis Hämatologie-Onkologie Dresden

Dresden, 01307, Germany

RECRUITING

Uniklinikum Erlangen, Strahlenklinik

Erlangen, 91054, Germany

RECRUITING

Universitätsmedizin Frankfurt, Klinik für Strahlentherapie und Onkologie

Frankfurt am Main, 60590, Germany

RECRUITING

UKGM Gießen, Klinik für Strahlentherapie

Giessen, 35392, Germany

RECRUITING

Universitätsklinikum Hamburg-Eppendorf, Zentrum für Onkologie; II. Medizinische Klinik und Poliklinik

Hamburg, 20246, Germany

NOT YET RECRUITING

Medizinische Hochschule Hannover (MHH), Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation

Hanover, 30625, Germany

NOT YET RECRUITING

Marien Hospital Herne, Klinik für Strahlentherapie und Radio-Onkologie

Herne, 44625, Germany

RECRUITING

Universitätsklinikum des Saarlandes, Klinik für Strahlentherapie und Radioonkologie

Homburg, 66421, Germany

RECRUITING

Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Klinik und Poliklinik für Radioonkologie der Strahlentherapie

Mainz, 55131, Germany

RECRUITING

Universitätsklinikum Münster, Klinik für Strahlentherapie - Radioonkologie

Münster, 48149, Germany

NOT YET RECRUITING

Universitätsklinikum Regensburg, Klinik und Poliklinik für Strahlentherapie

Regensburg, 93053, Germany

RECRUITING

CaritasKlinikum Saarbrücken St. Theresia, Klinik für Radioonkologie und Strahlentherapie

Saarbrücken, 66113, Germany

NOT YET RECRUITING

Klinikum St.-Elisabeth Straubing GmbH, Klinik für Hals-Nasen-Ohren-Heilkunde

Straubing, 94315, Germany

NOT YET RECRUITING

Klinikum Stuttgart, Klinik für Strahlentherapie und Radioonkologie

Stuttgart, 70174, Germany

RECRUITING

Universitätsklinikum Tübingen, Klinik für Radioonkologie

Tübingen, 72076, Germany

RECRUITING

Universitätsklinikum Ulm, Klinik für Hals- Nasen-Ohrenheilkunde, Kopf- und Halschirurgie

Ulm, 89075, Germany

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Radiotherapy; Cisplatin; pembrolizumab; Fluorouracil

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Studienzentrum der Klinik für Strahlentherapie und Radioonkologie

CONTACT

+49 6841 - 16 24688; repair.radonk@uks.eu

Markus Hecht, Prof. Dr. med.

CONTACT

+49 6841 - 16 24606; markus.hecht.clinicaltrials@uks.eu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2025
• First Posted: June 18, 2025
• Study Start: October 30, 2025
• Primary Completion (Estimated): December 1, 2032
• Study Completion (Estimated): December 31, 2032
• Last Updated: March 2, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (18)